2. MACROLIDE ANTIBIOTICS
⢠Group of antibiotics with a
macrocyclic lactone
structure to which one or
more deoxy sugars are
attached
⢠In 1950 the first drug of this
class was isolated:
Picromycin
⢠In 1952 Erythromycin and
Carbomycin were introduced
into clinic.
O
CH3
H3C
HO
CH3
HO
N
H3C
H3C
H3C
O
O
O
O
O
CH3
Picromycin
CH3
CH3
3. Macrolides: Erythromycin
⢠It was isolated from Streptomyces erythreus in 1952
⢠It was the first of these drugs to find clinical
application, both as a drug of choice and an
alternative to penicillin in individuals who are allergic
to β-lactam antibiotics
⢠Slightly water soluble
⢠Macrolides are stable in aqueous solutions at or
below room temperature. They are unstable in acidic
or basic conditions or at high temperatures.
4. Erythromycin: Mechanism of action
⢠Bacteriostatic at low but cidal at high concentrations
⢠Cidal action also depends on the organism and its
rate of multiplication
⢠More active in alkaline medium
⢠Acts by inhibiting bacterial protein synthesis
⢠Bind irreversibly to a site on the 50s subunit of the
ribosome and interferes with âtranslocationâ
5.
6. Erythromycin: Resistance
⢠Becoming a serious problem
⢠Several mechanisms are:
â Inability of organism to take up the antibiotic or presence of efflux
pump
â Decreased affinity
â Presence of plasmid associated erythromycin esterase
⢠Both clarithromycin and azithromycin show cross
resistance with erythromycin
⢠But telithromycin can be effective against macrolideresistant organisms
7. Pharmacokinetics
⢠Erythromycin base is acid labile but all others (newer)
are stable
⢠Given as enteric coated tablets
⢠Food delays absorption by retarding gastric emptying
⢠Its acid esters are better absorbed
⢠Widely distributed in the body except CSF
⢠Diffuses into prostatic fluid, accumulates in
macrophages
8. Pharmacokinetics
ContâŚ
⢠Concentrates in liver
⢠Inflammation allows greater tissue penetration
⢠70-80% plasma protein bound
⢠Partly metabolized and excreted primarily in the
active form (some enterohepatic circulation)
⢠Renal excretion is minor (5%)
⢠Its plasma t1/2 is 1.5hr, but it persists longer in
tissues
11. Uses
⢠As an alternative to pencillin
â Strep. Inf, Diptheria, Tetanus, Syphylis and Gonorrhoea
⢠As a first choice drug for:
â Atypical pneumania
â Whooping cough
â Chancroid
⢠As a second drug choice:
â
â
â
â
Campylobactor enteritis
Legionnaireâs pneumonia
Chlamydia trachomitis
Pencillin resistant Staphylococcal infections
12.
13. Roxithromycin
⢠Acid stable
⢠Good enteral absorption and tissue
penetration
⢠95% plasma protein bound
⢠Has longer half life 12hrs
14. Clarithromycin
⢠Acid stable
⢠Bioavailability is 50% due to first pass metabolism
⢠Follows zero order kinetics
⢠Longer half life (3-6hrs), its metabolite is also active
⢠Antibacterial spectrum is wider:
â Micobacterium avium complex
â M. leprae
â Toxoplasma gondii
15. Azithromycin
⢠Extended spectrum
⢠Better tolerability
⢠More active against H.influenza but less active
against gram possitive cocci
⢠Rapidly absorbed from empty stomach
⢠Longest half life (3days)
⢠Spectrum is identical to clarithromycin, except that it
is less active against Staphylococci and Streptococci
17. Clindamycin
⢠Mechanism of action is same as that of erythromycin
⢠Resistant mechanisms are same as those of
erythromycin
⢠It inhibits most of the gram possitive cocci
⢠Highly active against a vareity of anaerobes, specially
B. fragilis
⢠Aerobic gram negative bacilli are not effective
18. Clindamycin
ContâŚ
⢠Absorption is good
⢠Distributes well but not to CSF and brain
⢠Excreted in urine and bile
⢠Plasma half life is 3hrs
20. Vancomycin
⢠Glycopeptide antibiotic
⢠Discovered in 1956 as a pencillin substitute
⢠Effective against MRSA, Strep.viridans, enterococci
and clost.difficile
⢠Acts by inhibiting cell wall phospholipid synthesis as
well as peptidoglycon polymerization
(transglycolation step)
21. Vancomycin
Pharmacokinetics:
⢠No absorption from oral route
⢠Slow IV infusion is employed for treatment of
systemic infections or for prophylaxis
⢠Metabolism is minimal
⢠90-100% excreted through glomeruar filtration
ContâŚ
26. Linezolid
Restance:
⢠Decreased binding to the target site confers
resistance
Pharmacokinetics:
⢠Completely absorbed on oral administration
⢠IV preparations also available
⢠Widely distributed throughout the body
⢠Partly metabolized non enzymatically
⢠Excreted in urine
⢠Plasma half life is 5hrs
ContâŚ
28. Polypeptide Antibiotics
⢠Low molecular weight cationic polypeptide antibiotics
⢠All are powerful bactericidal agents
⢠Not used systemically due to toxicity
⢠All are produced by bacteria
⢠Clinically used ones are:
â Polymyxin B
â Colistin
â Bacitracin